Alterations in HIV-1 LTR promoter activity during AIDS progression
Alterations in HIV-1 LTR promoter activity during AIDS progression
复制标题
DOI：
10.1016/j.virol.2003.08.034
复制
发表时间：
2003-12-05
期刊：
影响因子：
3.7
通讯作者：
Kirchhoff, F
中科院分区：
文献类型：
--
作者：
Hiebenthal-Millow, K;Greenough, TC;Kirchhoff, F
与早期无症状感染期间的HIV-1变异相比，艾滋病患者中进化的HIV-1变异经常表现出增加的复制能力。众所周知，晚期HIV-1变异体通常表现出扩大的共受体趋向性和改变的Nef功能。在本研究中，我们研究了HIV-1 LTR启动子活性的增强是否也可能在疾病进展过程中进化。我们的研究结果表明，在12名hiv -1感染者中，有3人在艾滋病进展后LTR启动子活性增加。进一步的分析表明，U3核心增强子和交易反应（TAR）区域的多重改变似乎是功能活性增强的原因。我们的研究结果表明，在hiv -1感染个体的一个子集中，LTR转录增强有助于增加晚期病毒分离株的复制潜力，并可能加速疾病进展。(C) 2003 Elsevier Inc.版权所有。
HIV-1 variants evolving in AIDS patients frequently show increased replicative capacity compared to those present during early asymptomatic infection. It is known that late stage HIV-1 variants often show an expanded coreceptor tropism and altered Nef function. In the present study we investigated whether enhanced HIV-1 LTR promoter activity might also evolve during disease progression. Our results demonstrate increased LTR promoter activity after AIDS progression in 3 of 12 HIV-1-infected individuals studied. Further analysis revealed that multiple alterations in the U3 core-enhancer and in the transactivation-response (TAR) region seem to be responsible for the enhanced functional activity. Our findings show that in a subset of HIV-1-infected individuals enhanced LTR transcription contributes to the increased replicative potential of late stage virus isolates and might accelerate disease progression. (C) 2003 Elsevier Inc. All rights reserved.